基于代谢组学分析COPD肾虚痰瘀证与异常黑胆质证共性特征

 从代谢组学角度进行慢性阻塞性肺部疾病(COPD)中维西医病证结合的临床研究,解析中维医不同分型间及其与正常人群间代谢表型的构成差异,寻找并鉴定中维医证型的代谢生物标记物,阐述中医肾虚痰瘀证及维医异常黑胆质证在代谢组学方面的共性特征改变及其物质基础,以体现两者在代谢组学方面的交互性,为COPD的诊断、防治提供新的思路和方法奠定一定的基础。首先,按照纳入标准收集COPD稳定期患者105例,进行西医的诊断分级以及中医、维吾尔医的辨证分型,分为中医肾虚痰瘀证组和维医异常黑胆质证组,对所有患者及正常对照组受试者血样分批进行核磁共振技术(NMR)的代谢组学方面的测定和分析;得到健康人与各组COPD患者的血浆一维及二维氢谱,对1H-NMR谱进行分段积分后的积分值进行OPLS-DA分析,得到3D平面分布图,显示COPD患者肾虚痰瘀证组、异常黑胆质证组分别与正常对照组的分布区域完全分开,而中维医二组的分布区域未完全分开,说明两组血浆在代谢成分上无明显差异,同样表现为血桨中多种氨基酸显著降低,差异有统计学意义(P<0.05),其中包括异亮氨酸、亮氨酸、缬氨酸、丙氨酸、谷氨酰胺、酪氨酸、苯丙氨酸。此外,糖蛋白、不饱和脂类及极低密度脂蛋白也较健康人显著降低,差异有统计学意义(P<0.05);而乳酸、肉碱及丙酮、乙酰乙酸较健康人增高,差异有统计学意义(P<0.05);因此COPD二组中维医证患者血浆中代谢紊乱较正常对照组严重,提示氨基酸、蛋白质的代谢异常及脂肪代谢减弱、三大营养物质代谢反复相互影响的程度更重,使代谢紊乱状态更加严重。总之,从代谢组学角度出发,进行COPD中维医病证结合的对比研究,发现肾虚痰瘀证及异常黑胆质证患者代谢组学改变更突出,但两证的代谢组学变化基本一致,其生物表型相似,表现为氨基酸、脂肪及糖代谢异常,提示COPD肾虚痰瘀证与异常黑胆质证患者机体内三大物质代谢紊乱、能量代谢异常,相比健康人显示机体的免疫功能更低下、内分泌功能更紊乱、预后更差。

Common Characteristics of COPD of Traditional Chinese Medicine Kidney Depletion-phlegm-stasis Syndrome and Uygur Medicine Abnormal Savda Syndrome Based on Metabonomics

This paper studies the metabonomics change of COPD of the TCM types and the TUM types,through identifying the metabolic biological markers of the TCM kidney empty-phlegm-stasis syndrome and the Uygur medical abnormal savda syndrome, to guide the clinical diagnosis of COPD, and to provide some new ideas and methods. (1) A total of 105 cases of patients with COPD, diagnosed according to western medicine diagnosis classification, were chosen and divided two groups according to the TCM and the Uygur medicine on syndrome differentiation and classification. Meanwhile, a total of 52 healthy volunteers were chosen as the normal control group, from the medical center of the affiliated hospital of Chinese medicine, Xinjiang Medical University. (2) All blood samples of the subjects were tested through utilizing the NMR metabonomics; (3) The plasma 1H NMR spectra were analyzed using the orthogonal projection to the latent structure and the discriminant analysis (OPLS-DA) method with unit variance scaling. The discriminative significance of the metabolites was determined using the Pearson's product-moment correlation coefficient. 1H-NMR spectrum and 2D pattern recognition in the analysis show that for the COPD patients of the Kidney empty-phlegm-stasis syndrome group, and the abnormal savda syndrome in the normal control group, respectively, their distribution areas are separated completely, the metabolic components of plasma of the two group have a significant difference; but the metabolic components of the kidney empty-phlegm-stasis syndrome group and the abnormal black savda patients are not statistically different (P>0.05). The metabolism including the isoleucine, the leucine, the valine, the alanine, the tyrosine, the glutamine, the pheny-lalanine, is significantly reduced in level, and the lactic acid, the glycoprotein VLDL and the unsaturated fat are also significantly reduced. The carnitine is relatively higher, with a difference not statistically significant (P>0.05). Extremely low density lipoprotein plasma VLDL, the unsaturated lipid and acetone of the COPD kidney-empty-phlegm-stasis syndrome patients and the abnormal black savda patients are lower, but with a difference not statistically significant (P>0.05). So there are 14 kinds of the metabolites, which would expect to be serum specific biomarkers of the COPD kidney-empty-phlegm-stasis syndrome patients and abnormal savda patients. The results indicate that (1) the metabonomics change and the metabolic phenotype of the COPD with the kidney empty-phlegm-stasis syndrome and the abnormal savda syndrome are outstanding but similar, and also with common biomarkers, the material metabolic disorder, the low body's immune function, the endocrine disorders and the energy metabolism disorder are evident; (2) the metabonomics common features of the COPD with the TCM and the Uygur syndrome further reflect the interoperability of the two kinds of medical models of Chinese medicine, Uygur medicine and modern medicine about COPD; the COPD of syndrome differentiation would be more objective and more standard.